2-Methoxyisobutylisonitrile (MIBI) is a key starting material in the preparation of the complex technetium (99mTc) hexakis(2-methoxyisobutylisonitrile) (technetium (99mTc) Sestamibi). This radiopharmaceutical, which is commercially available in the form of a kit under the tradenames CARDIOLITE® and MIRALUMA®, is useful for detecting coronary artery disease as well as evaluating breast lesions by planar imaging. Discovered in 1981 by Alan Davison, it received FDA approval in 1990 and it has been sold commercially since February 1991.
The kit includes a lyophilized mixture of a copper complex of MIBI (tetrakis(2-methoxyisobutylisonitrile)copper(I) tetrafluoroborate ([Cu(MIBI)4]BF4)) as the active ingredient, sodium citrate dihydrate as a buffer, L-cysteine hydrochloride monohydrate as a stabilization aid, mannitol as a lyophilization aid, and stannous chloride dihydrate as a reducing agent. Prior to use, the lyophilized mixture is reconstituted with sodium pertechnetate (99mTc) and boiled to form technetium (99mTc) Sestamibi. The U.S. Pharmacopoeia (29th Ed.) requires that a mean of not less than 90% (corrected area percentage) of the total radioactivity is represented by 99mTc-Sestamibi, and a mean of not more than 5% (corrected area percentage) of the total radioactivity is present as 99mTc pentamibi dimethylvinyl isonitrile.
The synthesis of MIBI has been extensively studied over the past twenty five years. It is not readily achieved because there is no commercially available chemical having a related structure. Prior methods of preparing MIBI are described in U.S. Pat. Nos. 4,864,051, 4,988,827, 5,210,270 and 5,346,995.
However, there is a continuing need for improved methods of preparing MIBI and metal complexes thereof, such as [Cu(MIBI)4]BF4.